Abstract:

Chronic exposure to increased glucocorticoid concentrations
appears to lower the threshold for hippocampal neuronal degeneration
in the old rat. It has been proposed that increased
brain exposure to glucocorticoids may lower the threshold for
hippocampal neuronal degeneration in human aging and Alzheimer’s
disease. Here, we asked whether chronic administration
of high-dose cortisol to older nonhuman primates decreases
hippocampal neuronal number as assessed by
unbiased stereological counting methodology. Sixteen Macaca
nemestrina (pigtailed macaques) from 18 to 29 years of age
were age-, sex-, and weight-matched into pairs and randomized
to receive either high-dose oral hydrocortisone (cortisol)
acetate (4–6 mg/kg/d) or placebo in twice daily palatable treats
for 12 months. Hypothalamic–pituitary–adrenal activity was
monitored by measuring plasma adrenocorticotropin and cortisol,
24 hr urinary cortisol, and CSF cortisol. Urinary, plasma,
and CSF cortisol were elevated, and plasma adrenocorticotropin
was reduced in the active treatment group. Total hippocampal
volume, subfield volumes, subfield neuronal density,
and subfield total neuronal number did not differ between the
experimental groups. These findings suggest that chronically
elevated cortisol concentrations, in the absence of stress, do
not produce hippocampal neuronal loss in nonhuman primates.